A K_ATP channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias

Low concentrations of certain K<sub>ATP</sub> channel openers have been reported to exert a moderate inhibitory effect on arrhythmias during post-ischaemic early myocardial reperfusion, but the accompanying effects on the time course of changes in action potentials in intact hearts have not yet been studied. We report that in rat isolated hearts, reperfusion following 10 min of regional no-flow ischaemia was associated with both an acute, marked, but transient, shortening of ventricular repolarisation (by 63%) during reperfusion, and a high incidence (90%) of ventricular tachyarrhythmias. The K<sub>ATP</sub> channel opener Ro 31-6930 [2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide], delivered prior to ischaemia at a relatively low concentration (0.5 μM), significantly reduced the incidence and duration of reperfusion arrhythmias, and prevented the associated acute action potential shortening during reperfusion, each in a glibenclamide (1 μM)-sensitive manner (P<0.05, <i>n</i>=10–15 hearts). This was associated with a moderate and non-arrhythmogenic action potential shortening during ischaemia (a potentially “cardioprotective” effect). However, these data highlight the potential harm these drugs may cause, since a higher concentration of Ro 31-6930 caused marked shortening of action potentials and significant pro-arrhythmia during ischaemia

Do K_ATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K<sup>+</sup> (K<sub>ATP</sub>) channels open during the first 10 min of regional ischaemia in Langendorff-perfused rat hearts. Changes in monophasic action potentials and arrhythmias were studied during myocardial ischaemia in both the presence and absence of pharmacological K<sub>ATP</sub> modulation. Ligation of the left main coronary artery for 10 min did not shorten the action potential duration (APD). The APD<sub>50</sub> and APD<sub>80</sub> (15.5 +/- 1.0 and 38.1 +/- 2.3 ms, respectively [mean +/- S.E., n = 15 hearts], immediately prior to ligation) increased transiently during the first 4 min of ligation (by 160 and 79% respectively, P < 0.05), before returning to pre-ligation values, but without a significant below-baseline-shortening. The cardiac electrogram showed no accompanying ventricular tachyarrhythmia (VT). These results raised the possibility that the myocardial K<sub>ATP</sub> channels had not opened during the ligation. The K<sub>ATP</sub> opener Ro 31-6930 (0.5 and 5 microM) shortened the APD50 and APD80 during coronary ligation, to significantly below both their control and pre-occlusion values (P < 0.05), and caused a concentration-dependent increase in both the incidence and duration of VT during the ligation. Ro 31-6930 at 5 microM also shortened APD50 and APD80 even before ligation (by 50 and 62% respectively, P < 0.05), and abolished the normal APD-lengthening seen during ischaemia. The K<sub>ATP</sub> blocker glibenclamide (1 μM) abolished both the APD-shortening and pro-arrhythmic effects of the K<sub>ATP</sub> opener, both before and during coronary ligation, yet when delivered on its own, at the same concentration which abolished the effects of K<sub>ATP</sub> activation, it had no significant effect on the APD changes seen during the coronary ligation alone. These results suggest that, in Langendorff-perfused rat hearts in the absence of drugs, K<sub>ATP</sub> channels do not open during early myocardial ischaemia

Comment on `Measurement of the π+p⃗\pi^+ \vec p analyzing power at 68.3 MeV'

We comment on a recent paper by Weiser et al. [Phys. Rev. C {\bf 54}, 1930 (1996)]. The authors have performed a single-energy analysis of $\pi^+ p$ scattering data at 68.3 MeV, finding a value for the $S_{31}$ phase shift about 1^o smaller than found in the Karlsruhe-Helsinki (KH) partial-wave analysis. The authors use this result to argue for a dispersion relation analysis using recently measured data, so that their effect on the $\pi NN$ coupling constant (f^2) and $\Sigma$ amplitude can be determined. We note that these tasks were accomplished prior to the submission of the above paper. We clarify the effect of this new analyzing power data on f^2 and the $\Sigma$ amplitude.Comment: 5 pages of text. Revised according to Referee suggestion

Partial-Wave Analysis of Single-Pion Production Reactions

We present an overview of our efforts to analyze pion-nucleon elastic scattering data, along with data from related photo- and electroproduction reactions, in order to study the baryon spectrum. We then focus on the Delta(1232) resonance. Fits to pion photo- and electroproduction data have been used to extract values for the R_EM = E2/M1 and R_SM = S2/M1 ratios as functions of Q^2. These results are compared to other recent determinations.Comment: 7 pages, 9 figures, the Shape of Hadrons Workshop Proceedings (27-29 April, 2006 Athens, Greece